TY - JOUR
T1 - Spinal Nerve Tolerance to Single-Session Stereotactic Ablative Radiation Therapy
AU - Hrycushko, Brian
AU - van der Kogel, Albert J.
AU - Phillips, Lauren
AU - Folkert, Michael R
AU - Sayre, James W.
AU - Vernino, Steven
AU - Hassan-Rezaeian, Nima
AU - Foster, Ryan D
AU - Yamada, Yoshiya
AU - Timmerman, Robert
AU - Medin, Paul M.
N1 - Funding Information:
This project was funded by the Cancer Prevention & Research Institute of Texas. This project was funded by the Cancer Prevention & Research Institute of Texas. Disclosures: P.M., B.H., L.P., S.V., and R.F. were investigators and received salary support for this project funded by a research grant paid to their institution (University of Texas Southwestern Medical Center) from the Cancer Prevention & Research Institute of Texas. M.F. has received travel funding from Varian Medical Systems. Y.Y. has received payment for speaking engagements from Varian Medical Systems, Brainlab, Vision RT, and the Institute for Medical Education. Y.Y. is also on the Chordoma Foundation medical advisory board. R.T. is principal investigator of clinical research grants paid to his institution (University of Texas Southwestern Medical Center) from Varian Medical Systems, Elekta Oncology, and Accuray, Inc. P.M. teaches in radiosurgery courses sponsored by Brainlab.
Funding Information:
This project was funded by the Cancer Prevention & Research Institute of Texas .
Funding Information:
Disclosures: P.M., B.H., L.P., S.V., and R.F. were investigators and received salary support for this project funded by a research grant paid to their institution (University of Texas Southwestern Medical Center) from the Cancer Prevention & Research Institute of Texas. M.F. has received travel funding from Varian Medical Systems. Y.Y. has received payment for speaking engagements from Varian Medical Systems, Brainlab, Vision RT, and the Institute for Medical Education. Y.Y. is also on the Chordoma Foundation medical advisory board. R.T. is principal investigator of clinical research grants paid to his institution (University of Texas Southwestern Medical Center) from Varian Medical Systems, Elekta Oncology, and Accuray, Inc. P.M. teaches in radiosurgery courses sponsored by Brainlab.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/7/15
Y1 - 2019/7/15
N2 - Purpose: This study was performed to determine the dose-related incidence of neuropathy from single-session irradiation of the C6-C8 spinal nerves using a pig model and to test the hypothesis that the spinal nerves and spinal cord have the same tolerance to full cross-sectional irradiation. Methods and Materials: Twenty-five Yucatan minipigs received study treatment. Each animal underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 1.5-cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. Pigs were distributed into 5 groups with prescription doses of 16 (n = 7), 18 (5), 20 (5), 22 (5), or 24 (3) Gy with corresponding maximum nerve doses of 17.3, 19.5, 21.6, 24.1, and 26.2 Gy. The neurologic status of all animals was followed for approximately 52 weeks by serial electrodiagnostic examination and daily observation of gait. Histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff staining was performed on bilateral spinal nerves and the spinal cord. Results: Marked gait change was observed in 15 of the 25 irradiated pigs. Affected animals presented with a limp in their left front limb, and electromyography demonstrated evidence of denervation in C6 and C7 innervated muscles. Probit analysis showed the ED50 for gait change after irradiation of the spinal nerves to be 19.7 Gy (95% confidence interval, 18.5-21.1). The latency for all responding pigs was 9 to 15 weeks after irradiation. All symptomatic pigs had demyelination and fibrosis in their irradiated nerves, whereas contralateral nerves and spinal cord were normal. Conclusions: The ED50 for symptomatic neuropathy after full cross-sectional irradiation of the spinal nerves was found to be 19.7 Gy. The dose response of the C6-C8 spinal nerves is not significantly different from that of full cross-sectional irradiation of the spinal cord as observed in companion studies.
AB - Purpose: This study was performed to determine the dose-related incidence of neuropathy from single-session irradiation of the C6-C8 spinal nerves using a pig model and to test the hypothesis that the spinal nerves and spinal cord have the same tolerance to full cross-sectional irradiation. Methods and Materials: Twenty-five Yucatan minipigs received study treatment. Each animal underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 1.5-cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. Pigs were distributed into 5 groups with prescription doses of 16 (n = 7), 18 (5), 20 (5), 22 (5), or 24 (3) Gy with corresponding maximum nerve doses of 17.3, 19.5, 21.6, 24.1, and 26.2 Gy. The neurologic status of all animals was followed for approximately 52 weeks by serial electrodiagnostic examination and daily observation of gait. Histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff staining was performed on bilateral spinal nerves and the spinal cord. Results: Marked gait change was observed in 15 of the 25 irradiated pigs. Affected animals presented with a limp in their left front limb, and electromyography demonstrated evidence of denervation in C6 and C7 innervated muscles. Probit analysis showed the ED50 for gait change after irradiation of the spinal nerves to be 19.7 Gy (95% confidence interval, 18.5-21.1). The latency for all responding pigs was 9 to 15 weeks after irradiation. All symptomatic pigs had demyelination and fibrosis in their irradiated nerves, whereas contralateral nerves and spinal cord were normal. Conclusions: The ED50 for symptomatic neuropathy after full cross-sectional irradiation of the spinal nerves was found to be 19.7 Gy. The dose response of the C6-C8 spinal nerves is not significantly different from that of full cross-sectional irradiation of the spinal cord as observed in companion studies.
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U2 - 10.1016/j.ijrobp.2019.03.044
DO - 10.1016/j.ijrobp.2019.03.044
M3 - Article
C2 - 30953713
AN - SCOPUS:85065163379
SN - 0360-3016
VL - 104
SP - 845
EP - 851
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 4
ER -